The Role of Hormones in Postpartum Mood Disorders

March 26, 2024 updated by: National Institute of Mental Health (NIMH)

An Endocrine Model for Postpartum Mood Disorders

Determine whether postpartum depression is triggered by the abrupt withdrawal of estrogen and progesterone.

The appearance of mood and behavioral symptoms during pregnancy and the postpartum period has been extensively reported. While there has been much speculation about possible biologically based etiologies for postpartum disorders (PPD), none has ever been confirmed. Preliminary results from two related studies (protocols 90-M-0088, 92-M-0174) provide evidence that women with menstrual cycle related mood disorder, but not controls, experience mood disturbances during exogenous replacement of physiologic levels of gonadal steroids. The present protocol is designed to create a "scaled-down" hormonal milieu of pregnancy and the puerperium in order to determine whether women who have had a previous episode of postpartum major effective episode will experience differential mood and behavioral effects compared with controls and to determine whether it is the abrupt withdrawal of gonadal steroids or the prolonged exposure to gonadal steroids that is associated with mood symptoms. Supraphysiologic plasma levels of gonadal steroids will be established, maintained, and then rapidly reduced, simulating the hormonal events that occur during pregnancy and parturition. This will be accomplished by administering estradiol and progesterone to women who are pretreated with a gonadotropin releasing hormone (GnRH) agonist (Lupron). After eight weeks, administration of gonadal steroids will be stopped in one group of patients and controls, and a sudden decline in the plasma hormone levels will be precipitated. Another group will be maintained on supraphysiologic levels of estrogen and progesterone for an additional month. Outcome measures will include mood, behavioral and hormonal parameters (a separate protocol done in collaboration with NICHD).

Study Overview

Status

Recruiting

Conditions

Postpartum Depression

Intervention / Treatment

Detailed Description

The appearance of mood and behavioral symptoms during pregnancy and the postpartum period has been extensively reported. While there has been much speculation about possible biologically based etiologies for postpartum disorders (PPD), none has ever been confirmed. Preliminary results from two related studies (protocols 90-M-0088, 92-M-0174) provide evidence that women with menstrual cycle related mood disorder, but not controls, experience mood disturbances during exogenous replacement of physiologic levels of gonadal steroids. The present protocol is designed to create a scaled-down hormonal milieu of pregnancy and the puerperium in order to determine whether women who have had a previous episode of postpartum major affective episode will experience differential mood and behavioral effects compared with controls and to determine whether it is the abrupt withdrawal of gonadal steroids or the prolonged exposure to gonadal steroids that is associated with mood symptoms. Supraphysiologic plasma levels of gonadal steroids will be established, maintained, and then rapidly reduced, simulating the hormonal events that occur during pregnancy and parturition. This will be accomplished by administering estradiol and progesterone to women who are pretreated with a gonadotropin releasing hormone (GnRH) agonist (Lupron). After eight weeks, administration of gonadal steroids will be stopped in one group of patients and controls, and a sudden decline in the plasma hormone levels will be precipitated. Another group will be maintained on supraphysiologic levels of estradiol and progesterone for an additional month. Outcome measures will include mood, behavioral, and hormonal parameters.

Study Type

Interventional

Enrollment (Estimated)

100

Phase

Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: Peter J Schmidt, M.D.
Phone Number: (301) 496-6120
Email: peterschmidt@mail.nih.gov

Study Locations

United States
- Maryland
  - Bethesda, Maryland, United States, 20892
    - Recruiting
    - National Institutes of Health Clinical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

Yes

Description

INCLUSION CRITERIA:

A. Group 1: Women with a history of postpartum depression:

A history of DSM-IV major depression or hypomanic/manic episode that occurred within three months of childbirth (as determined by a SCID interview);
has been well for a minimum of one year;
a regular menstrual cycle for at least three months;
age 18-50;
not pregnant, not lactating and in good medical health;
medication free (including birth control pills);
no history of puerperal suicide attempts or psychotic episodes requiring hospitalization.

B. Group 2: Women with a history of Major Depressive Disorder

A history of DSM-IV major depression episode(s) occurring outside of pregnancy and not within three months postpartum;
has been well for a minimum of one year;
a regular menstrual cycle for at least three months;
age 18-50;
not pregnant, not lactating and in good medical health;
medication free (including birth control pills);
no history of suicide attempts or psychotic episodes requiring hospitalization.

C. Group 3: Normal Controls

Controls will meet all criteria specified except they must not have any past or present Axis I diagnosis or evidence of menstrually related mood disorders.
EXCLUSION CRITERIA:
Patients will not be permitted to enter this protocol if they have important clinical or laboratory abnormalities including any history of the following:
endometriosis;
undiagnosed enlargement of the ovaries;
liver disease;
breast cancer;
a history of blood clots in the legs or lungs;
undiagnosed vaginal bleeding;
porphyria;
diabetes mellitus;
malignant melanoma;
gallbladder or pancreatic disease;
heart or kidney disease;
cerebrovascular disease (stroke);
cigarette smoking;
a history of suicide attempts or psychotic episodes requiring hospitalization;
recurrent migraine headaches;
pregnancy (patients will be warned not to become pregnant during the study and will be advised to employ barrier contraceptive methods;
pregnancy-related medical conditions such as hyperemesis gravidarum, pretoxemia and toxemia, deep vein thrombosis (DVT) and bleeding diathesis;
Any woman with a first degree relative (immediate family) with premenopausal breast cancer or breast cancer presenting in both breasts or any woman who has multiple family members (greater than three relatives) with postmenopausal breast cancer will also be excluded from participating in this protocol;
Any woman meeting the Stages of Reproductive Aging Workshop Criteria (STRAW) for the perimenopause will be excluded from participation. Specifically, we will exclude any woman with an elevated plasma FSH level (greater than or equal to 14 IU/L) and with menstrual cycle variability of > 7 days different from their normal cycle length;
Subjects who are unable to provide informed consent;
NIMH employees and staff and their immediate family members will be excluded from the study per NIMH policy.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Interventional Model: Parallel Assignment
Masking: Double

Number of Arms

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Group 1, Hormone and Placebo Group 8 weeks of hormonal addback plus 4 weeks of placebo	Drug: Estradiol To determine whether it is abrupt withdrawal or prolonged exposure to gonadal steroids that is associated with PPD. Other: Placebo To determine whether it is abrupt withdrawal or prolonged exposure to gonadal steroids that is associated with PPD. Drug: Progesterone To determine whether it is abrupt withdrawal or prolonged exposure to gonadal steroids that is associated with PPD.
Active Comparator: Group 2, Continued Replacement Group 12 weeks of hormone addback	Drug: Estradiol To determine whether it is abrupt withdrawal or prolonged exposure to gonadal steroids that is associated with PPD. Drug: Progesterone To determine whether it is abrupt withdrawal or prolonged exposure to gonadal steroids that is associated with PPD.

Participant Group / Arm